High Risk of Venous Thromboembolism in Klinefelter Syndrome

Background- Klinefelter syndrome (KS) is the most common sex chromosome disorder. The genetic background is the extra X chromosome. Venous thromboembolism (VTE) has been observed among KS patients. The aim of the present study was to examine whether KS is associated with VTE. Methods and Results- We followed up all hospital in-and outpatients (N=1085) in Sweden with a diagnosis of KS between January 1, 1969, and December 31, 2010, for diagnosis of VTE. The reference population was the total male populace of Sweden. We calculated standardized incidence ratios for VTE, adjusted for age, sex, education, time period, and region of residence. The standardized incidence ratio for KS was 6.43 (95% CI 5.15-7.93), with the highest ratio observed at young age. The standardized incidence ratios for VTE were 12.10 (95% CI 6.22-21.21) before age 30 years, 11.00 (95% CI 7.86-14.99) between ages 30 and 49 years, 4.83 (95% CI 3.23-6.95) between ages 50 and 69 years, and 2.07 (95% CI 0.74-4.53) for ages >= 70 years. The cumulative incidence of VTE for KS patients was 8.6% at age 50 years and 20.8% at age 70 years. Conclusions- KS is associated with high risk of VTE. KS could be considered a genetic hypercoagulable state. This has clinical implications for the prevention and diagnosis of VTE among patients with KS.